We have described the influence of selected factors that increase the toxicity of nanoplastics (NPs) and microplastics (MPs) with regard to cell viability, various types of cell death, reactive oxygen species (ROS) induction, and genotoxicity. These factors include plastic particle size (NPs/MPs), zeta potential, exposure time, concentration, functionalization, and the influence of environmental factors and cell type. Studies have unequivocally shown that smaller plastic particles are more cytotoxic, penetrate cells more easily, increase ROS formation, and induce oxidative damage to proteins, lipids, and DNA. The toxic effects also increase with concentration and incubation time. NPs with positive zeta potential are also more toxic than those with a negative zeta potential because the cells are negatively charged, inducing stronger interactions. The deleterious effects of NPs and MPs are increased by functionalization with anionic or carboxyl groups, due to greater interaction with cell membrane components. Cationic NPs/MPs are particularly toxic due to their greater cellular uptake and/or their effects on cells and lysosomal membranes. The effects of polystyrene (PS) vary from one cell type to another, and normal cells are more sensitive to NPs than cancerous ones. The toxicity of NPs/MPs can be enhanced by environmental factors, including UV radiation, as they cause the particles to shrink and change their shape, which is a particularly important consideration when working with environmentally-changed NPs/MPs. In summary, the cytotoxicity, oxidative properties, and genotoxicity of plastic particles depends on their concentration, duration of action, and cell type. Also, NPs/MPs with a smaller diameter and positive zeta potential, and those exposed to UV and functionalized with amino groups, demonstrate higher toxicity than larger, non-functionalized and environmentally-unchanged particles with a negative zeta potential.

The widespread presence of polystyrene nanoparticles (PS-NPs) in the human body has raised concerns about their potential biological toxicity. When assessing the safety of nanoparticles and other xenobiotics, a key aspect is their effect on blood cells, particularly erythrocytes, which experience the most direct exposure to nanoparticles circulating in the bloodstream. The present study evaluated the impact of non-functionalized PS-NPs with diameters of ∼30 nm, ∼45 nm, and ∼70 nm on human red blood cells after 24 hours of incubation. The studied PS-NPs did not influence intracellular Ca²⁺ ion levels or caspase 3 activity, and did not induce phosphatidylserine translocation at pre-hemolytic concentrations (below 100 µg/mL). Moreover, exposure did not increase intracellular ROS levels at any of the tested concentrations, suggesting that generalized intracellular oxidative stress is likely not the primary mechanism underlying the effects induced by PS-NPs in human erythrocytes. However, the observed increase in lipid peroxidation, detected from 50 µg/ml, indicates that oxidative damage at the membrane level may contribute to the overall toxic response. The results suggest that PS-NPs interact primarily with the erythrocyte membrane, leading to membrane destabilization associated with increased calpain activity, observed already at a concentration of 1 µg/mL, and enhanced lipid peroxidation. It is noteworthy that the most pronounced changes were induced by the smallest nanoparticles (∼30 nm), suggesting a size-dependent effect on erythrocyte integrity. These findings suggest that PS-NP toxicity in erythrocytes is mediated mainly through red blood cell membrane destabilization rather than classical intracellular oxidative stress alone.